| 吴华为,吴佳妮,张辰嘉,陈志凌.咽喉宁雾化剂通过调控上皮-间质转化抑制鼻黏膜重塑治疗嗜酸粒细胞性慢性鼻窦炎[J].浙江中西医结合杂志,2026,36(4): |
| 咽喉宁雾化剂通过调控上皮-间质转化抑制鼻黏膜重塑治疗嗜酸粒细胞性慢性鼻窦炎 |
| Yanhouning Nebulizer Inhibits Nasal Mucosal Remodeling in Eosinophilic Chronic Rhinosinusitis by Regulating Epithelial–Mesenchymal Transition |
| 投稿时间：2025-10-31 修订日期：2026-03-09 |
| DOI： |
| 中文关键词: 咽喉宁雾化剂 酸粒细胞性慢性鼻窦炎 上皮-间质转化 TGF-β1/Smad3信号通路 鼻黏膜重塑 |
| 英文关键词:Yanhouning Nebulizer Eosinophilic chronic rhinosinusitis Epithelial–mesenchymal transition TGF-β1/Smad3 signaling pathway Nasal mucosal remodeling |
| 基金项目:浙江省中医药科技计划项目（2024ZL659） |
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| 中文摘要: |
| 目的：探讨咽喉宁雾化剂是否通过调控上皮-间质转化（EMT）过程影响鼻黏膜重塑，从而明确治疗嗜酸粒细胞性慢性鼻窦炎（ECRS）的作用及其分子机制。方法：采用卵清蛋白联合氢氧化铝致敏雌性BALB/c小鼠建立ECRS模型，将造模成功小鼠随机分为模型组、咽喉宁雾化剂低、中、高剂量组、阳性药（布地奈德）组，并设立对照组，给与相应干预。通过苏木精-伊红染色与马松三色染色分别评估鼻黏膜组织嗜酸性粒细胞（EOS）浸润情况与胶原沉积情况；ELISA法检测血清中转化生长因子-β1（TGF-β1）、白细胞介素-4（IL-4）、白细胞介素-5（IL-5）及基质金属蛋白酶-9（MMP-9）等细胞因子水平；免疫组化观察鼻黏膜组织中E-钙黏蛋白（E-cadherin）、波形蛋白（Vimentin）、α-平滑肌肌动蛋白（α-SMA）等EMT相关蛋白表达；蛋白免疫印迹检测TGF-β1/SMAD家族成员3（Smad3）通路关键蛋白表达变化。结果：与对照组相比，模型组小鼠鼻黏膜出现显著上皮增生、纤毛结构紊乱、杯状细胞增生及大量炎症细胞浸润，伴明显胶原沉积，表明ECRS模型构建成功。药物干预后，各治疗组鼻黏膜病理损伤均得到改善，EOS浸润[（21.00 ± 4.36）、（11.33 ± 1.53）、（7.00 ± 1.00）、（7.67 ± 2.08）比（42.67 ± 3.21），P＜0.05]及胶原沉积[（1.68 ± 0.22）、（1.38 ± 0.37）、（1.01 ± 0.11）比（3.05 ± 0.66），P＜0.01]显著减少；咽喉宁雾化剂可显著降低小鼠血清中TGF-β1 [（43.79 ± 6.80）、（38.30 ± 3.88）比（56.58 ± 8.18），P＜0.05]、IL-4 [（80.92 ± 7.62）、（54.75 ± 11.40）比（108.46 ± 15.85），P＜0.01]、IL-5 [（63.10 ± 8.29）、（39.84 ± 4.45）、（30.77 ± 6.72）比（99.92 ± 10.05），P＜0.01]和MMP-9 [（157.73 ± 16.29）、（123.22 ± 12.98）比（232.75± 23.75），P＜0.01]水平；免疫组化与蛋白免疫印迹结果进一步表明，该制剂能有效上调E-cadherin [（0.22 ± 0.03）、（0.25 ± 0.02）比（0.15 ± 0.01），P＜0.01]表达，下调Vimentin [（0.23 ± 0.00）、（0.21 ± 0.01）、（0.19 ± 0.01）比（0.25 ± 0.01），P＜0.05]与α-SMA [（0.17 ± 0.02）比（0.27 ± 0.02），P＜0.01]表达，并抑制TGF-β1 [（2.40 ± 0.22）、（1.72 ± 0.10）比（3.40 ± 0.30），P＜0.01]和p-Smad3 [（2.09 ± 0.18）、（1.23 ± 0.07）比（3.16 ± 0.06），P＜0.05]蛋白的活化。结论：咽喉宁雾化剂能够通过抑制TGF-β1/Smad3信号通路活性，调控EMT进程，减轻鼻黏膜组织重塑及嗜酸粒细胞浸润，从而发挥对ECRS的治疗作用。 |
| 英文摘要: |
| Objective: To investigate whether Yanhouning Nebulizer exerts therapeutic effects on eosinophilic chronic rhinosinusitis (ECRS) by regulating epithelial–mesenchymal transition (EMT)-mediated nasal mucosal remodeling and to explore its underlying molecular mechanisms. Methods: ECRS model was established in female BALB/c mice sensitized with ovalbumin combined with aluminum hydroxide. Successfully modeled mice were randomly divided into model group, low-dose, medium-dose, and high-dose Yanhouning Nebulizer groups, positive control (budesonide) group, and control group was established and given corresponding intervention. Eosinophil (EOS) infiltration and collagen deposition in nasal mucosa were evaluated by hematoxylin-eosin and Masson staining, respectively. Serum levels of Transforming Growth Factor-beta 1 (TGF-β1), Interleukin-4 (IL-4), Interleukin-5 (IL-5), and Matrix Metalloproteinase-9 (MMP-9) were measured by ELISA. Expression of EMT-related proteins (Epithelial Cadherin (E-cadherin), Vimentin, Alpha-Smooth Muscle Actin (α-SMA)) in nasal mucosa was detected by immunohistochemistry, and key proteins of the TGF-β1/SMAD family member 3 (Smad3) pathway were analyzed by Western blot. Results: Compared with the control group, the model group exhibited significant epithelial hyperplasia, disordered ciliary structure, goblet cell hyperplasia, massive inflammatory cell infiltration, and marked collagen deposition, indicating successful ECRS modeling. After drug intervention, all treatment groups showed improved nasal mucosal pathology, significantly reduced EOS infiltration [(21.00 ± 4.36)、(11.33 ± 1.53)、(7.00 ± 1.00)、(7.67 ± 2.08)vs. (42.67 ± 3.21)，P＜0.05]and collagen deposition [(1.68 ± 0.22)、(1.38 ± 0.37)、(1.01 ± 0.11)vs. (3.05 ± 0.66)，P＜0.01]. Yanhouning Nebulizer significantly decreased serum levels of TGF-β1 [(43.79 ± 6.80)、(38.30 ± 3.88)vs. (56.58 ± 8.18)，P＜0.05], IL-4 [(80.92 ± 7.62)、(54.75 ± 11.40)vs. (108.46 ± 15.85)，P＜0.01], IL-5 [(63.10 ± 8.29)、(39.84 ± 4.45)、(30.77 ± 6.72)vs. (99.92 ± 10.05)，P＜0.01], and MMP-9 [(157.73 ± 16.29)、(123.22 ± 12.98)vs. (232.75± 23.75)，P＜0.01]. Immunohistochemistry and Western blot results further demonstrated that the nebulizer upregulated E-cadherin expression [(0.22 ± 0.03)、(0.25 ± 0.02)vs. (0.15 ± 0.01)，P＜0.01], downregulated Vimentin [(0.23 ± 0.00)、(0.21 ± 0.01)、(0.19 ± 0.01)vs. (0.25 ± 0.01)，P＜0.05]and α-SMA expression [(0.17 ± 0.02)vs. (0.27 ± 0.02)，P＜0.01], and inhibited the activation of TGF-β1 [(2.40 ± 0.22)、(1.72 ± 0.10)vs. (3.40 ± 0.30)，P＜0.01]and p-Smad3 [(2.09 ± 0.18)、(1.23 ± 0.07)vs. (3.16 ± 0.06)，P＜0.05] proteins. Conclusion: Yanhouning Nebulizer alleviates ECRS by suppressing the TGF-β1/Smad3 signaling pathway, regulating EMT, and reducing nasal mucosal remodeling and eosinophil infiltration. |
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